High-Throughput Assessment of Drug Cardiac Safety Using a High-Speed Impedance Detection Technology-Based Heart-on-a-Chip

Zhang, Xi; Wang, Tianxing; Wang, Ping; Hu, Ning

doi:10.3390/mi7070122

Cited by 45 publications

(30 citation statements)

References 28 publications

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“…Zhang et al [84] introduced the heart-on-a-chip device that used high-speed impedance detection to assess cardiac drug efficacy. The device records the contraction of CMs to reveal drug effects.…”

Section: Heart-on-a-chipmentioning

confidence: 99%

Organ-on-a-chip: recent breakthroughs and future prospects

et al. 2020

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BackgroundMicrofluidics is a science and technology that precisely manipulates and processes microscale fluids. It is commonly used to precisely control microfluidic (10 −9 to 10 −18 L) fluids using channels that range in size from tens to hundreds of microns and is known as a "lab-on-a-chip" [1][2][3][4]. The microchannel is small, but has a large surface area and high mass transfer, favoring its use in microfluidic technology applications including low regent usage, controllable volumes, fast mixing speeds, rapid responses, and precision control of physical and chemical properties [1,5,6]. Microfluidics integrate sample preparation, reactions, separation, detection, and basic operating units such as cell culture, sorting and cell lysis [7]. For these reasons, interest in OOAC has intensified [8]. OOAC combines a range of chemical, biological and material science disciplines [9] and was selected as one of the "Top Ten Emerging Technologies" in the World Economic Forum [10].OOAC is a biomimetic system that can mimic the environment of a physiological organ, with the ability to regulate key parameters including AbstractThe organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. Through a combination of cell biology, engineering, and biomaterial technology, the microenvironment of the chip simulates that of the organ in terms of tissue interfaces and mechanical stimulation. This reflects the structural and functional characteristics of human tissue and can predict response to an array of stimuli including drug responses and environmental effects. OOAC has broad applications in precision medicine and biological defense strategies. Here, we introduce the concepts of OOAC and review its application to the construction of physiological models, drug development, and toxicology from the perspective of different organs. We further discuss existing challenges and provide future perspectives for its application.

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Section: Heart-on-a-chipmentioning

confidence: 99%

Organ-on-a-chip: recent breakthroughs and future prospects

et al. 2020

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“…The free Ca 2+ then binds to troponin and activates myosin attachment to the actin filament, pulling the latter to the center of the sarcomere to complete a mechanical contraction [ 167 ]. Zhang et al assessed this phenomenon in their OoC system [ 168 ] by means of a high-speed impedance detection technology based on a nonconductive substrate with a pattern of 16 interdigitated electrodes (IDEs) to culture primary neonatal rat cardiomyocytes (NRCM) monolayers and to record the rapid impedance fluctuations induced by their beating [ 169 ]. Administration of verapamil, an L-type calcium channel blocker, which reduces calcium influx and action potential duration, resulted in a recorded decrease in the beating rate and contractility of cardiomyocytes, demonstrating the suitability of their heart-on-a-chip to evaluate drug effect.…”

Section: Biosensors For Measuring Ooc’ Electromechanical Activitymentioning

confidence: 99%

Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems

et al. 2020

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Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

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“…Contractile properties of cells, especially cardiomyocytes for heart-on-a-chip platforms is of great importance and it is reported to be affected by intracellular calcium secretion. Hence, it is important to measure the calcium levels for heart-on-a-chip platforms (56,57).…”

Section: Sensors To Monitor Cell Behaviormentioning

confidence: 99%